Making disubstituted acetic acids from 2-(saturated hydrocarbon substituted) cyclohexanols



Patented Aug. 8, 1950 MAKING DISUBSTITUTED ACE-TIC ACIDS FROM 2(SATURATED .HYDROCARBON SUBSTITUTED) CYCLOHEXANOLS Earl L. Pelton andAndrew A. Holzschuh, Midland,

Mich, assignors to The Dow Chemical Company, Midland, Mich., acorporation of Delaware No Drawing. Application J anuary 3, 1949, SerialNo. 69,037

7 Claims. (01. 260-531)- This invention relates to a method for thepreparation of di-(saturated hydrocarbon) substituted acetic acids, andespecially the a-(saturated hydrocarbon substituted) caproic acids from2-(saturated hydrocarbon substituted) cyclohexanols, and to certain newcompounds soproduced.

One of us has described, in U. S. Patent 1,961,623, the reaction ofcyclohexanol with an excess of a fused alkali metal hydroxide to producea mixture of acids, one of which has the empirical formula C12H20O2.Later work has shown this acid to be 2-cyclohexene-l-caproic acid. Ithas been proven that the production of 2 cyclohexene-l-caproic acid bythe caustic fusion and oxidation of cyclohexanol requires the existenceof an intermediate condensate, 2-(2-cyc10- hexene) cyclohexanol, so thatthe reaction proceeds as follows, with the point of oxidative scissionbeing indicated by a dotted line:

We have now found that the point of scission in the saturated, analogouscompound, Z-cyclohexane cyclohexanol, and in Z-(saturated hydrocarbonsubstituted) cyclohexanols generally,is not the same as that shown inthe foregoing equation, and that, instead of forming the expectedcyclohexane caproic acid or analogous hydrocarbon caproic acids when 2-(saturated hydrocarbon substituted) cyclohexanols are fused with anexcess of caustic alkali, there are produced as principal productsoz-CYClOhEXELIlE caproic acid or the analogous a-(saturated hydrocarbonsubstituted) caproic acid. The reaction is set forth in the followingequation, with the point of oxidative scis- H (j; R-JJ-C O OH H: CH2(KOH) HZ'CHTCHTCHZ The products are seen to be di-(saturatedhydrocarbon) substituted acetic acids.

The fOllOWil'lg examples illustrate the practice of the invention.

Example 1 630 grams (10 moles) of per cent potassium hydroxide as mixedwith grams (1 mole) of potassium acetate to lower the viscosity of themixture when molten, and the mixture was placed in a nickel pot 6 inchesin diameter and 10 inches deep. The pot was provided with a stirrer anda cover having an inlet for liquid feed and a vapor outlet connectedwith a condenser. The pot was heated to 350 C. and the stirrer was setin motion. In the course of 6 hours, there was introduced dropwise intothe fused akali about 1800 grams (9.88 moles) of Q-cyclohexane cycloehexanol. One-half hour after the cyclohexyl cyclohexanol had all beenadded, heating and stirring were discontinued and the reaction mixturewas cooled, then dissolved in water and acidified with hydrochloricacid. The organic layer was separated from the resulting brine, and theorganic acid product was distilled. The main product was not theanticipated cyclohexane ca.- proic acid whose melting point is known tobe 32-33 0;, nor was it 2-cyclohexene-l-caproic acid, freezing at 11 C.,but was, instead. a colorless oil boiling at 167 to 172 C. at 10millimeters, absolute pressure. This acid had a neutralizationequivalent of 196.2 and did not freeze or crystallize at temperaturesdown to -20 C. It was a saturated product, as shown by its failure toabsorb bromine. The acid readily formed an amide melting at 177.8 to178.3 C., and an ethyl ester boiling about l30-135 C. at 10 millimeters.Since these properties resemble those of the cyclohexyl butyl aceticacid (oz-CYClOhGXBJlB caproic acid) reported by von Braun and Kurtz,Ber. deutsch. chem. Gesell. 70, 1224-29 (1937), some of their reportedacid was synthesized from malonic ester. The so-formed a-cyclohexanecapro-ic acid was converted to the corresponding amide which melted at178.7 to 179.6 C. A miX-' ture of the amides from the two sources meltedat 178 to 178.9 0., showing that the product obtained from the causticfusion is a-cyclohexane caproic acid. The dialkylamin-o ethanol ester ofthis acid has given indication of utility as an antihistaminic. The freeacid also forms useful highboiling esters.

It is apparent that the present, one-step process for producingw-cyclohexane caproic acid in yields of 50 to 80 per cent in a few hoursis preferable to the old process which involved the suc cessivepreparations of diethyl malonate, its sodium reaction product,cyclohexyl diethyl ma1onate, its sodium reaction product, cyclohexylbutyl diethyl malonate, cyclohexyl butyl malonic acid, and finallycyclohexyl butyl acetic acid (acyclohexane caproic acid), since the oldsynthesis is tedious, expensive, and gives low over-all yields.

Example 2 In a similar manner, 30 pounds of potassium hydroxide and 30pounds of sodium acetate were mixed and fused at a temperature of 350 C.in an iron kettle 2 feet in diameter and 3 feet deep, fitted with aneffective stirrer. 2-secondary-butyl cyclohexanol was introduced througha feed pipe passing through the tight-fitting cover of the kettle atsuch a rate that 29% pounds had been consumed in 10 hours. The reactionmass was cooled, dissolved in water and acidified, and 28 pounds of anacidic organic oil was recovered. This oil was distilled and gave a 40per cent yield of a-secondarybutyl caproic acid, boiling at 135 C. under10 millimeters and at 158 C. at 30 millimeters of mercury, absolutepressure. This compound has a density (25/4 C.) of 0.9060 and arefractive index (25/D) of 1.4342. It forms an amide melting at114.9-115.2 C. There was also obtained a 29 per cent yield ofasecondarybutyl cyclohexanebutyric acid, boiling at about 169 C. at 10millimeters pressure.

Example 3 In the same apparatus and under the same conditions describedin Example 2, 38 pounds of 2-isopropyl cyclohexanol formed 35 per centof the theoretical yield of oc-iSODIODYl caproic acid, boiling at 109 C.at 5 millimeters pressure and at 125 C. at millimeters pressure. Thisnew compound has a density (25/4 C.) of 0.9017 and a refractive index(25/D) of 1.4270. It forms an amide melting at 123-123.3 C. There wasalso obtained 13 per cent of 2-isopropyl cyclohexanebutyric acid and 15per cent of a,2-dli$0 propyl cyclohexene caproic acid.

The alkali metal hydroxide used in the present reaction may be thepotassium hydroxideacetate mixtures of the various examples, or it maybe potassium or sodium hydroxide alone, or mixtures of these hydroxides,as disclosed, for

example, in a prior Pelton Patent 1,961,623, or in Grether and PeltonPatent 2,010,692, or in Pelton and Holzschuh Patent 2,425,343. Thepreferred temperatures of reaction for the present process are from 290to 375 C., though any temperature which causes scission of thecyclohexanol nucleus may be used. Temperatures below 290 C. are usuallynot satisfactory.

The a- (saturated hydrocarbon substituted) caproic acids made by thepresent method are useful as intermediates in the preparation ofantihistaminics, antispasmodics, germicides and other pharmaceuticals,as well as in the preparation of new and useful high boiling esters.

We claim:

1. The method for the production of a-(saturated hydrocarbonsubstituted) caproic acids which consists essentially in heating a2-(saturated hydrocarbon substituted) cyclohexanol with a fused alkalimetal hydroxide at a temperature in the range from 290 to 375 C.

2. The method for the production of a-alkyl Y caproic acids whichconsists essentially in heating a 2-alkyl cyclohexanol with a fusedalkali metal hydroxide at a temperature in the range from 290 to 375 C.

3. The method for the production of a-CYCIO- hexane caproic acid whichconsists essentially in heating 2-cyclohexane cyclohexanol with a fusedalkali metal hydroxide at a temperature in the range from 290 to 375 C.

4. The method for the production of a-GYCIO- hexane caproic acid whichconsists essentially in heating Z-cyclohexane cyclohexanol with fusedpotassium hydroxide at a temperature in the range from 290 to 375 C.

5. The method for the production of a-cyclohexane caproic acid whichconsists essentially in heating 2-cyclohexane cyclohexanol with a fusedmixture of about 10 moles of potassium hydroxide for each mole ofpotassium acetate, at a temperature in the range from 290 to 375 C.

6. The method for the production of a-secondarybutyl caproic acid whichconsists essentially in heating a-secondarybutyl cyclohexanol with afused alkali metal hydroxide at a temperature in the range from 290 to375 C.

7. The method for the production of a-iSO- propyl caproic acid whichconsists essentially in heating 2-isopropyl cyclohexanol with a fusedalkali metal hydroxide at a temperature in the range from 290 to 375 C.

EARL L. PELTON. ANDREW A. HOLZSCHUH.

REFERENCES CITED The following references are of record in the file ofthis patent:

Fischer et a1: Ber. Deut. Chem, vol. 45, pp. 250-253 (1912).

Sommaire: Beilstein (Handbuch, 4th ed.) vol. 2, 2nd suppl., page 308(1942) I. G. Farben: Beilstein (Handbuch, 4th ed.). vol. 2, 2nd suppl.,page 313 (1942).

1. THE METHOD FOR THE PRODUCTION OF A-(SATURATED HYDROCARBONSUBSTITUTED) CAPROIC ACIDS WHICH CONSISTS ESSENTIALLY IN HEATING A2-(SATURATED HYDROCARBON SUBSTITUTED) CYCLOHEXANOL WITH A FUSED ALKALIMETAL HYDROXIDE AT A TEMPERATURE IN THE RANGE FROM 290* TO 375*C.